Thrombotic Disorders

Question 1

What is venous thromboembolism?

Answer 1

Venous thromboembolism is the process of blood clot formation in the veins.

Question 2

What is the difference between provoked and unprovoked VTE?

Answer 2

Provoked VTE is associated with a clear precipitating cause from history or tests, while unprovoked VTE has no clear cause.

Question 3

What is thrombophilia?

Answer 3

Thrombophilia refers to a condition where the blood in the body clots more easily than normal.

Question 4

What are the causes of circulatory stasis, a component of Virchow’s triad?

Answer 4

Causes of circulatory stasis include bed rest, lower limb orthopedic surgery, major abdominal surgery, pregnancy, and long haul flights/long car journeys.

Question 5

What are the causes of hypercoagulable states?

Answer 5

Causes of hypercoagulable states include smoking, oestrogens (oral contraceptives, HRT), active cancer, and inherited and acquired thrombophilias.

Question 6

What are the causes of vascular injury, another component of Virchow’s triad?

Answer 6

Causes of vascular injury include limb trauma (including surgery), foreign bodies (e.g., IV cannulae, pacemaker wires), sepsis (bacteria, toxins), and previous DVT (deep vein thrombosis). May-Thurner Syndrome is also a cause of vascular injury.

Question 7

What is the most common inherited thrombophilia?

Answer 7

The most common inherited thrombophilia is Factor V Leiden, which is caused by a mutation of the Factor V gene.

Question 8

What is the second most common inherited thrombophilia?

Answer 8

The second most common inherited thrombophilia is prothrombin thrombophilia, caused by a Factor II gene mutation.

Question 9

What are some other forms of inherited thrombophilias?

Answer 9

Other inherited forms of thrombophilia include protein C deficiency, protein S deficiency, hereditary anti-thrombin deficiency, and congenital dysfibrinogenemia.

Question 10

When should testing for inherited thrombophilias be considered?

Answer 10

Testing for hereditary thrombophilia should be considered in individuals who have had unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) and have a first-degree relative who also had DVT or PE, especially if there is a plan to stop anticoagulation treatment.

Question 11

Should thrombophilia testing be routinely offered to first-degree relatives of people with a history of DVT or PE and thrombophilia?

Answer 11

No, routine thrombophilia testing should not be offered to first-degree relatives of people with a history of DVT or PE and thrombophilia.

Question 12

Should testing for hereditary thrombophilia be offered to people who are already on anticoagulation treatment?

Answer 12

No, testing for hereditary thrombophilia should not be offered to people who are already on anticoagulation treatment.

Question 13

Should thrombophilia testing be offered to people who have had provoked DVT or PE?

Answer 13

No, thrombophilia testing should not be offered to people who have had provoked DVT or PE.

Question 14

What is the most common acquired thrombophilia?

Answer 14

The most common acquired thrombophilia is antiphospholipid syndrome, which is an autoimmune disorder where antibodies attack phospholipids.

Question 15

What is the gender distribution of antiphospholipid syndrome?

Answer 15

Antiphospholipid syndrome is more commonly seen in females, with approximately 70% of cases occurring in women.

Question 16

What is the association between antiphospholipid syndrome and Systemic Lupus Erythematosus (SLE)?

Answer 16

Approximately 10-15% of people with Systemic Lupus Erythematosus have antiphospholipid syndrome.

Question 17

What are the increased risks of pregnancy complications in individuals with antiphospholipid syndrome?

Answer 17

Individuals with antiphospholipid syndrome have an increased risk of miscarriage, stillbirth, and pre-eclampsia.

Question 18

What is the second most common acquired thrombophilia?

Answer 18

The second most common acquired thrombophilia is acquired dysfibrinogenemia, which can be caused by conditions such as severe liver disease, autoimmune disease (e.g., rheumatoid arthritis), plasma cell dyscrasias (e.g., myeloma), and certain cancers (e.g., cervical cancer).

Question 19

What is the common clinical presentation of deep vein thrombosis (DVT)?

Answer 19

Clinically, DVT may present with unilateral calf swelling, heat, pain, redness, and hardness. However, it is important to note that there can be no signs or symptoms in some cases.

Question 20

What is the most common site of deep vein thrombosis (DVT)?

Answer 20

The most common site of DVT is in the calf, particularly in the popliteal and tibial veins. DVT can also occur in the thigh, involving the femoral and iliac veins.

Question 21

What are some differential diagnoses for deep vein thrombosis (DVT)?

Answer 21

Some differential diagnoses for DVT include Baker’s cyst, cellulitis, and muscular pain.

Question 22

What are the risk factors associated with DVT?

Answer 22

Risk factors for DVT include a history of previous DVT, immobility, surgery, pregnancy, cancer, obesity, and certain medical conditions such as thrombophilias.

Question 23

What is the D-dimer test used for in the investigation of DVT?

Answer 23

The D-dimer test is useful to rule out DVT if the clinical probability is low. It measures the level of D-dimer, a breakdown product of fibrin, which is elevated in venous thromboembolism.

Question 24

What is the investigation of choice for DVT?

Answer 24

Doppler ultrasound is the investigation of choice for DVT. It provides real-time 2D images and uses color Doppler (Duplex) to show the direction and velocity of blood flow. Thrombosed veins appear non-compressible on ultrasound.

Question 25

When is contrast venography rarely required in the investigation of DVT?

Answer 25

Contrast venography is rarely required but can be useful in extensive disease or when looking for anatomical malformations.

Question 26

What is the significance of D-dimer in DVT diagnosis?

Answer 26

D-dimer is a breakdown product from fibrin, the fibrous mesh component of blood clots. It is only present when the coagulation system has been activated. An elevated D-dimer level is seen in venous thromboembolism. A negative D-dimer test can be used to rule out DVT or PE if the clinical probability is low. However, a positive D-dimer test is not diagnostic on its own.

Question 27

Are there any limitations of the D-dimer test?

Answer 27

Yes, the D-dimer test is very sensitive but not very specific. Occasionally, it can be negative in cases of large or extensive DVTs or PEs. Therefore, it should not be used if there is a high clinical probability of DVT or PE.

Question 28

What is the treatment approach for DVT limited to the calf?

Answer 28

For DVT limited to the calf, symptomatic treatment is provided. Repeat ultrasound is done in 7 days to ensure no progression of the clot.

Question 29

How is ilio-femoral DVT treated?

Answer 29

Ilio-femoral DVT is treated with anticoagulation using Direct Oral Anticoagulants (DOACs) such as Rivaroxaban or Dabigatran. The duration of anticoagulation is 3-6 months for the first event and lifelong for the second event. Warfarin may be used in cases of renal dysfunction.

Question 30

When should thrombophilia testing be considered in the treatment of DVT?

Answer 30

Thrombophilia testing should be considered if there is a first-degree relative with a history of venous thromboembolism (VTE).

Question 31

What are the clinical presentations of pulmonary embolism (PE)?

Answer 31

The clinical presentation of PE can vary depending on the size and location of the emboli. Microemboli are often asymptomatic. Small, peripheral emboli may present with pleuritic pain, breathlessness, and haemoptysis. Large, central emboli can cause chest pain, breathlessness, and hypoxia. Massive emboli can lead to syncope, shock, tachycardia, and even death.

Question 32

What are some diagnostic findings in pulmonary embolism (PE)?

Answer 32

In PE, oxygen saturations are typically low, and blood gas analysis shows a low PaO2. Electrocardiogram (ECG) may reveal sinus tachycardia (fast heart rate) and characteristic findings such as S1, QIII, TIII. An echocardiogram may show signs of right heart strain.

Question 33

What is CTPA, and when is it used in the diagnosis of PE?

Answer 33

CTPA stands for CT pulmonary angiogram, which is a CT scan used to visualize the pulmonary arteries and detect blood clots. CTPA carries a high radiation dose and is typically used if there is a reasonable likelihood of PE. However, it is important to consider alternative approaches in some groups of patients.

Question 34

What is the Wells score used for in the investigation of PE?

Answer 34

The Wells score is a scoring system used to assess the probability of PE. It helps guide the decision-making process regarding further investigations.

Question 35

How is a low probability of PE investigated?

Answer 35

In cases of low probability of PE, a D-dimer test is performed first. If the D-dimer test is positive, indicating a possible clot, a CTPA may be conducted to confirm the diagnosis.

Question 36

What is a ventilation-perfusion lung scan?

Answer 36

A ventilation-perfusion (V/Q) lung scan is a nuclear medicine test that involves inhaled and injected radioisotopes. It assesses the mismatch between lung ventilation and perfusion, helping to detect areas of the lung with abnormal blood flow. However, its use may be limited in the presence of underlying lung disease.

Question 37

When is a ventilation-perfusion lung scan used in the diagnosis of PE?

Answer 37

A ventilation-perfusion lung scan is used as an alternative to CTPA when CTPA is contraindicated. This includes situations such as severe contrast allergy, severe renal dysfunction, or a high risk from radiation exposure.

Question 38

What factors should be considered when choosing anticoagulation therapy for PE treatment?

Answer 38

When selecting anticoagulation therapy for PE treatment, it is important to consider co-morbidities, contraindications, and patient preferences. Assessing bleeding risk using a scoring system such as HASBLED can help guide decision-making.

Question 39

What are some special circumstances to consider in PE treatment?

Answer 39

Special circumstances in PE treatment include renal function, body weight extremes, cancer-associated thrombosis, and antiphospholipid syndrome (APLS).

Question 40

What is the initial treatment for large PE?

Answer 40

For large PE, initial treatment typically involves the administration of heparin, usually subcutaneous low molecular weight heparin (e.g., Enoxaparin).

Question 41

How long is anticoagulation therapy continued after a PE?

Answer 41

Following a first event of PE, anticoagulation therapy is usually continued for 3-6 months. In the case of a second event or persistent risk factors (e.g., thrombophilia), lifelong anticoagulation may be necessary.

Question 42

Can smaller PEs be treated with direct oral anticoagulants (DOACs) without initial heparin therapy?

Answer 42

Yes, smaller PEs can be treated directly with DOACs without the need for initial heparin therapy.

Question 43

What treatment options are available for massive PE?

Answer 43

Treatment for massive PE includes intravenous fluids, intravenous heparin infusion, and consideration of thrombolysis. Thrombolysis may be considered if the patient is in shock or shows signs of right heart strain. Other options include surgical embolectomy or catheter fragmentation.

Question 44

What are some measures for VTE prevention?

Answer 44

VTE prevention measures include prophylactic low-dose subcutaneous heparin, low-dose Rivaroxaban after major joint surgery, venous compression stockings, pneumatic compression stockings, early mobilization, and maintaining good hydration.

Question 45

What is the role of von Willebrand factor (vWF) in platelet adhesion?

Answer 45

vWF acts as a molecular bridge between platelets and exposed collagen, facilitating platelet adhesion.

Question 46

How do platelets become activated?

Answer 46

Platelets become activated through various interactions, including the binding of vWF to glycoprotein 1b-IX-V complexes, leading to platelet tethering and rolling along the endothelial surface.

Question 47

What is the function of glycoprotein 2b/3a (GP2b3a) on platelets?

Answer 47

GP2b3a on activated platelets binds to fibrinogen, facilitating platelet aggregation and clustering.

Question 48

What is the role of thromboxane A2 in platelet function?

Answer 48

Thromboxane A2, generated from arachidonic acid under the influence of cyclooxygenase, promotes platelet activation, aggregation, and adhesion by binding to thromboxane receptors on other platelets.

Question 49

What are the main uses of antiplatelet medications?

Answer 49

Antiplatelets are used to prevent or treat conditions involving excessive platelet activation, such as atherosclerosis, coronary artery disease, and stroke.

Question 50

What is the mechanism of action of antiplatelet drugs?

Answer 50

Antiplatelet drugs inhibit platelet function by targeting various pathways, such as blocking the activation of glycoprotein 2b/3a receptors or inhibiting the production of thromboxane A2.

Question 51

What are some common side effects of antiplatelet medications?

Answer 51

Common side effects of antiplatelets may include increased risk of bleeding, gastrointestinal disturbances, allergic reactions, and bruising.

Question 52

What are the common side effects of aspirin?

Answer 52

Peptic ulceration, rash, and high doses may cause hearing loss/tinnitus. In children given aspirin for viral illness, it can lead to brain and liver damage.

Question 53

What is the mechanism of action of aspirin?

Answer 53

Aspirin irreversibly inhibits Cyclooxygenase 1 (COX 1), blocking the production of prostaglandins and thromboxanes. It is an irreversible inhibitor of COX 1, while non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen are reversible inhibitors.

Question 54

What is the effect of aspirin on platelet function?

Answer 54

Aspirin decreases the production of thromboxane, which reduces its binding to the thromboxane receptor. This leads to decreased platelet adhesion, activation, and aggregation. However, high doses of aspirin can inhibit the production of both thromboxane and prostacyclin, which may counteract the desired inhibition of platelet aggregation.

Question 55

What are the main uses of aspirin?

Answer 55

Aspirin is commonly used in patients with established vascular diseases such as ischemic heart disease (myocardial infarction, angina), cerebrovascular disease, and peripheral vascular disease. It improves prognosis, reduces mortality, and decreases adverse events like heart attacks and strokes.

Question 56

What is the significance of aspirin as a drug?

Answer 56

Aspirin is considered a mainstay drug due to its affordability and effectiveness in preventing and managing various cardiovascular conditions.

Question 57

What is the mechanism of action of Clopidogrel?

Answer 57

Clopidogrel is a platelet P2Y12 receptor inhibitor. It blocks the binding of ADP to the P2Y12 receptor on platelets, thereby reducing platelet aggregation, activation, and adhesion.

Question 58

What is the use of Clopidogrel?

Answer 58

Clopidogrel is used as part of dual antiplatelet therapy (DAPT) following a myocardial infarction (MI) or elective coronary stenting. It is also used as a first-line treatment for peripheral arterial disease and in patients with recurrent stroke despite aspirin therapy.

Question 59

What are the side effects of Clopidogrel?

Answer 59

The main side effects of Clopidogrel include bleeding, which can affect the timing of major surgeries, and rash. It is important to note that up to 30% of individuals may not achieve the full effect of the drug, leading to potential Clopidogrel resistance.

Question 60

What is the role of Glycoprotein IIb/IIIa receptor inhibitors, such as Tirofiban?

Answer 60

Glycoprotein IIb/IIIa receptor inhibitors act on the final common pathway of platelet aggregation. These drugs are highly potent anti-thrombotic agents but carry a high risk of bleeding. They are typically given during high-risk coronary stent procedures and primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) and high-risk coronary anatomy.

Question 61

What is the mechanism of action of Warfarin?

Answer 61

Warfarin inhibits the production, specifically gamma carboxylation, of vitamin K-dependent coagulation factors 2, 7, 9, and 10. It also inhibits the production of natural anticoagulants protein C and S.

Question 62

What are the clinical uses of Warfarin?

Answer 62

Warfarin is the drug of choice for patients with mechanical heart valves and mitral stenosis with atrial fibrillation. However, it is being superseded by direct oral anticoagulants (DOACs) for stroke prophylaxis in atrial fibrillation, treatment of deep vein thrombosis (DVT), and pulmonary embolism (PE).

Question 63

What are the main side effects of Warfarin?

Answer 63

The main side effect of Warfarin is bleeding, which can be managed with slow reversal using vitamin K or rapid reversal using blood factors like prothrombin complex concentrate or fresh frozen plasma. Warfarin is also known to be teratogenic, crossing the placenta and posing a significant concern, particularly in the first trimester. Other side effects include warfarin-induced skin necrosis and a transient hypercoagulable state during warfarin induction, requiring overlap with heparin.

Question 64

What is the mechanism of action of Heparin?

Answer 64

Heparin enhances the effect of the natural anticoagulant antithrombin (AT). It binds to AT and activates it, leading to the inhibition of coagulation factors 2, 7, 9, 10, 11, and 12.

Question 65

How is the therapeutic effect of Heparin measured?

Answer 65

The therapeutic effect of Heparin can be measured by monitoring the activated partial thromboplastin time (APTT), which reflects the activity of the intrinsic pathway. The goal is to achieve an APTT that is 1.5-2.5 times the control value.

Question 66

What are the side effects of Heparin?

Answer 66

The main side effect of Heparin is bleeding. The antidote for Heparin overdose is protamine, which acts as a potent vasodilator.

Question 67

What is the role of unfractionated Heparin?

Answer 67

Unfractionated Heparin is still used in specific situations such as chronic kidney disease, dialysis, and bypass machines where its use is warranted.

Question 68

What are low molecular weight heparins (LMWHs)?

Answer 68

Low molecular weight heparins, such as Enoxaparin and Tinzaparin, are given subcutaneously and have reliable absorption. They do not require monitoring. These drugs are used acutely for conditions such as myocardial infarction (MI), atrial fibrillation (AF), pulmonary embolism (PE), iliofemoral deep vein thrombosis (DVT), and for venous thromboembolism (VTE) prophylaxis.

Question 69

What is Heparin-induced thrombocytopenia (HIT)?

Answer 69

Heparin-induced thrombocytopenia is a potentially dangerous side effect of heparin therapy. It is more common with unfractionated heparin (UFH) than with low molecular weight heparins (LMWH). HIT is caused by antibodies that bind to complexes of heparin and platelet factor 4 (PF4), leading to platelet activation and a prothrombotic state. It is characterized by a falling platelet count and can result in the extension of a previously diagnosed blood clot or the formation of new blood clots elsewhere, including skin necrosis.

Question 70

What are DOACs?

Answer 70

DOACs (Direct Oral Anticoagulants) are a class of anticoagulant medications. Examples include Rivaroxaban and Apixaban, which are factor Xa inhibitors, and Dabigatran, which is a direct thrombin inhibitor.

Question 71

What are the main uses and advantages of DOACs?

Answer 71

DOACs are used for various indications such as treating deep vein thrombosis (DVT), pulmonary embolism (PE), and atrial fibrillation (AF). They are also used for post-hip/knee replacement prophylaxis. DOACs offer more reliable anticoagulant action than warfarin. Higher doses provide greater effectiveness with similar bleeding risks, while lower doses maintain efficacy while reducing the risk of bleeding. DOACs also have fewer drug interactions compared to warfarin. Dabigatran has an antidote called Idarucizumab, while Rivaroxaban and Apixaban have an antidote called Andexanet.

Question 72

What are the main treatments for haemophilia?

Answer 72

The main treatments for haemophilia involve the use of recombinant factor VIII or factor IX infusions. These infusions aim to raise the levels of the deficient clotting factor to 50-100% of normal. Prophylactic infusions are administered every 2-3 days, while on-demand infusions are given when bleeding or injury occurs. Gene therapy, using a modified virus to introduce a copy of the gene that encodes for the missing clotting factor, is also being explored as a treatment option.

Question 73

What are the main treatments for von Willebrand disease (vWD)?

Answer 73

The treatment options for vWD include the use of desmopressin (DDAVP), which increases the synthesis and release of von Willebrand factor (vWF) and factor VIII. Anti-fibrinolytics, such as tranexamic acid, can be used to reduce thrombus breakdown. Plasma products can also be administered to replace vWF and factor VIII.

Question 74

How is vitamin K used in the treatment of bleeding disorders?

Answer 74

Vitamin K is used to treat vitamin K deficiency and to reverse the effects of warfarin, an anticoagulant medication. Vitamin K is administered in cases of fat malabsorption, biliary obstruction, haemorrhagic disease of the newborn (given 1mg at birth), and in patients receiving warfarin treatment. Vitamin K is essential for the gamma carboxylation of vitamin K-dependent factors, including factors X, IX, VII, II, as well as proteins S and C.